Preparation and HPLC applications of rigid macroporous organic polymer monoliths

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    J. Sep. Sci. 2004, 27, 747766 i 2004WILEY-VCH Verlag GmbH&Co. KGaA,Weinheim

    Frantisek Svec

    Department of Chemistry,University of California, Berkeley,CA 94720-1460, USA

    Preparation and HPLC applications of rigidmacroporous organic polymermonoliths

    Rigid porous polymer monoliths are a new class of materials that emerged in theearly 1990s. These monolithic materials are typically prepared using a simple moldingprocess carried out within the confines of a closed mold. For example, polymerizationof a mixture comprising monomers, free-radical initiator, and porogenic solventaffords macroporous materials with large through-pores that enable applications in arapid flow-through mode. The versatility of the preparation technique is demonstratedby its use with hydrophobic, hydrophilic, ionizable, and zwitterionic monomers. Sever-al system variables can be used to control the porous properties of the monolith overa broad range and to mediate the hydrodynamic properties of the monolithic devices.A variety of methods such as direct copolymerization of functional monomers, chemi-cal modification of reactive groups, and grafting of pore surface with selected polymerchains is available for the control of surface chemistry. Since all the mobile phasemust flow through the monolith, the convection considerably accelerates mass trans-port within the molded material, and the monolithic devices perform well, even at veryhigh flow rates. The applications of polymeric monolithic materials are demonstratedmostly on the separations in the HPLC mode, although CEC, gas chromatography,enzyme immobilization, molecular recognition, advanced detection systems, andmicrofluidic devices are also mentioned.

    Key Words: Polymeric monoliths; Preparation; Modification; Application; Stationary phase; Sep-aration; HPLC; CEC;

    Received: January 20, 2004; revised: April 20, 2004; accepted: April 20, 2004

    DOI 10.1002/jssc.200401721

    1 Introduction

    Monoliths are separation media in the format that can becompared to a single large particle that does not containinterparticular voids typical of packed beds. The firstattempts to make single-piece separation media dateback to the late 1960s and early 1970s. For example,highly swollen monolithic polymer gel was prepared by

    free-radical polymerization of an aqueous solution of 2-hydroxyethyl methacrylate with 0.2% ethylene dimeth-acrylate (crosslinking monomer), inserted into a glasstube, and used for size-exclusion chromatography in 1967[1]. Unfortunately, the effectiveness of fractionation wasrather low. Another early approach involved open-porepolyurethane foams prepared in situ [25]. In contrast tothe hydrogel, the permeability of these monoliths wasexcellent. However, excessive swelling in some solventsand softness were deleterious characteristics that pre-vented their successful use in both liquid and gas chroma-tography. Macroporous discs [69] and compressed softpolyacrylamide gels [10] placed in a cartridge or columnrepresent other examples of monolithic materials. Theseelegant approaches have been described in detail in aseries of excellent review articles [1116]. The early1990s saw the development of another category of rigidmacroporousmonoliths formed by a very simple moldingprocess in which a mixture of monomers and solvent waspolymerized and immediately used within a closed tube orother container under carefully controlled conditions [17].Since porous inorganic materials are very popular sup-ports widely used in catalysis and chromatography [18],monoliths prepared from silica were developed almostsimultaneously with the organic polymers [19, 20].

    Correspondence: Frantisek Svec, Department of Chemistry,University of California, Berkeley, CA 94720-1460, USA.Phone: +1 510 643 3168. Fax: +1 510 643 3079.E-mail:

    Abbreviations: HPLC, high performance liquid chromatography;CEC, capillary electrochromatography; PEEK, poly(ether-ether-ketone); AMPS, 2-acrylamido-2-methyl-1-propanesulfonic acid;GMA, glycidyl methacrylate; VAL, 2-vinyl-4,4-dimethylazlactone;ST styrene; BuMA, butyl methacrylate; NIPAAm, N-isopropyl-acrylamide; AIBN, 2,29-azobisisobutyronitrile; TEMPO, 2,2,6,6-tetramethyl-1-pyperidinyloxy; carboxy-TEMPO, 4-carboxy-2,2,6,6-tetramethyl-1-piperidinyloxy; carboxy-PROXYL, 3-car-boxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy; TEMED, N,N,N,N-tet-ramethylethylenediamine; DEAE, diethylaminoethyl; THF, tetra-hydrofuran; HIC, hydrophobic interaction chromatography;LCST, lower critical solution temperature; ESI MS, electrosprayionization mass spectrometry; IP-RP-HPLC, ion-pair reversed-phase high-performance liquid chromatography; ODS, octade-cylsilica; SEC, size-exclusion chromatography.

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    Detailed accounts of these materials have been publishedrecently [16, 2123] and the newest developments arepresented elsewhere in this issue.

    2 Macroporous polymersMacroporous polymers emerged in the late 1950s as aresult of the search for polymeric matrices suitable for themanufacture of ion-exchange resins with better osmoticshock resistance and faster kinetics. The history of theseinventions has been reviewed a short time ago [24]. Incontrast to the polymers that require solvent swelling tobecome porous, macroporous polymers are characterizedby a permanent porous structure formed during their prep-aration that persists even in the dry state. Their internalstructure consists of numerous interconnected cavities(pores) of different sizes, and their structural rigidity issecured through extensive crosslinking. These polymersare typically produced as spherical beads by a suspensionpolymerization process [2527]. To achieve the desiredporosity, the polymerization mixture should contain both acrosslinking monomer and an inert diluent, the poro-gen [2831]. Solvating or non-solvating solvents for thepolymer that is formed, supercritical carbon dioxide, orsoluble non-crosslinked polymers or mixtures of suchpolymers and solvents have proven to be efficient poro-gens.

    Macroporous polymers are finding numerous applicationsas both commodity and specialty materials. The formercategory includes ion-exchangers and adsorbents, sup-ports for solid phase synthesis, polymeric reagents, andcatalysts, while chromatographic packings fit well into thelatter [32]. Although the vast majority of current macropor-ous beads are based on styrene-divinylbenzene copoly-mers, other monomers including acrylates, methacry-lates, vinylpyridines, vinylpyrrolidone, and vinyl acetatehave also been utilized [32].

    While the suspension polymerization that affords macro-porous polymers has already been analyzed in the litera-ture many times [2731], little was known until recently onhow to prepare macroporous polymers by bulk polymeri-zation within amold [17, 33, 34].

    2.1 Preparation of rigid polymermonoliths

    The preparation of rigid macroporous organic polymersproduced by a facile molding process is simple andstraightforward. The mold, typically a tube, is sealed atone end, filled with a polymerization mixture, and thensealed at the other end. The polymerization is then trig-gered, often by heating in a bath at a temperature of 55808C [17, 35, 36]. In addition to thermally initiated poly-merization, redox initiation has also been used [37].Another option, UV light initiation, can only be carried outin UV transparent molds such as glass tubes, fused silica

    capillaries, and microfluidic chips [3841]. The seals arethen removed, the tube is provided with fittings, attachedto a pump, and a solvent is pumped through the monolithto remove the porogens and any other soluble compoundsthat remained in the pores after the polymerization wascompleted. A broad variety of tube sizes and materials,such as stainless steel, poly(ether-ether-ketone) (PEEK),glass, plastic microchips, and fused silica capillaries havebeen used as molds for the preparation of monoliths [37,38, 4050].

    While the preparation of cylindrical monoliths with a homo-geneous porous structure in capillaries and tubes up to adiameter of about 1025 mm is readily achieved in a sin-gle polymerization step, larger size monoliths are some-what more difficult to prepare. Dissipation of the heat ofpolymerization is frequently slow and the exotherm maybe sufficient to increase substantially the reaction tem-perature, significantly accelerate the polymerization, andcause a rapid decomposition of the initiator. If this processis not controlled, monoliths with unpredictable radial andaxial gradients of porosity are obtained [44]. However, theslow and gradual addition of the polymerization mixture tothe reaction vessel in which the polymerization reactionproceeds continuously minimizes the heat production andallows the preparation of very large diameter monolithswith homogeneous porous structures. Another elegantmethod that helps to solve the problem of heat dissipationhas been demonstrated recently [51]. Using analysis ofthe heat release during the polymerization, Podgornik atal. derived a mathematical model for the prediction of themaximum thickness of the monolith that can be preparedin a single step without affecting the radial homogeneity ofthe material. To obtain large cylindrical objects, theseauthors prepared a few annular monoliths with variouswell-defined outer and inner diameters that inserted oneinto another to form a monolith with the desired largevolume. These radial flow columns extend the monolithictechnology to the field of scaled-up preparative separa-tions [52].

    Buchmeiser et al. presentedanatypical approach tomono-lithic columns [5356]. They used ring-opening meta-thesis copolymerization of norborn-2-ene and 1,4,4a,5,8,8a-hexahydro-1,4,5,8-exo,endo-dimethanonaphthalenewithin borosilicate glass columns in the presence of poro-genic solvents such as toluene, methylene chloride,methanol, and 2-propanol to obtain functionalized mono-lithic materials. A ruthenium catalyst was used to preparemonolithic separation media with typical macroporousmorphology. By variation of the polymerization conditions,such as the ratio ofmonomers, the porogenic solvents, andthe temperature, the pore size could be varied within abroad range of 230 lm, affording materials with specificsurfaceareas in a rangeof 60210 m2/g.

    J. Sep. Sci. 2004, 27, 747766 i 2004WILEY-VCH Verlag GmbH&Co. KGaA,Weinheim

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    2.2 Control of porous properties

    Many applications of porous materials in areas such ascatalysis, adsorption, ion exchange, chromatography,and solid phase synthesis rely on the intimate contact witha surface that supports the active sites. In order to obtaina large surface area, a significant number of smaller poresshould be incorporated into the polymer. The most sub-stantial contribution to the overall surface area comesfrom micropores, with sizes smaller than 2 nm, followedby the mesopores ranging from 2 to 50 nm. Larger pores(macropores) contribute very little to the surface area.However, these pores are essential to allow liquid to flowthrough the material at a reasonably low pressure. Thispressure, in turn, depends on the overall porous proper-ties of the material [36]. Therefore, the pore size distribu-tion of the monolith must be adjusted properly to fit eachtype of application.

    The pore size distribution of the molded monoliths is quitedifferent from those observed for classical macroporousbeads. An extensive study of the types of pores obtainedduring polymerization both in suspension and in anunstirred mold has revealed that, in contrast to commonwisdom, there are some important differences betweenthe suspension polymerization used for the preparation ofbeads and the bulk-like polymerization process utilized forthe preparation of molded monoliths [35]. An example ofpore size distribution curves and the internal morpholo-gies recorded for both beads and monolith are shown inFigure 1. The morphology of the monolith featuring indivi-dual microglobules and their irregular clusters is similar tothat found for beads [57]. However, the size of the clustersand the irregular voids between them is much larger in themonolith. In the case of polymerization in an unstirredmold the most important differences compared to suspen-sion are the lack of interfacial tension between the aque-

    ous and organic phases, and the absence of dynamicforces that are typical of stirred dispersions. The morphol-ogy of the monoliths is closely related to their porous prop-erties, and is also a direct consequence of the quality ofthe porogenic solvent as well as the percentage of cross-linking monomer and the ratio between the monomer andporogen phases. The presence of synergistic effects ofthese reaction conditions was verified using multivariateanalysis [38].

    The porosity and flow characteristics of macroporouspolymer monoliths intended for use as separation mediafor chromatography, flow-through reactors, catalysts, orsupports for solid phase chemistry have to be adjustedduring their preparation. Key variables such as tempera-ture, composition of the pore-forming solvent mixture, andcontent of crosslinking monomer allow the tuning of theaverage pore size within a broad range spanning at leasttwo orders of magnitude from tens to thousands of nano-meters [34, 36, 58]. The scanning electron micrographs ofFigure 2 represent examples of the porous structures ofpoly(glycidyl methacrylate-co-trimethylolpropane tri-methacrylate) monoliths prepared using various polymeri-zation conditions [38].

    The choice of pore-forming solvent (porogen) is themostly used tool for the control of porous properties with-out changing the chemical composition of the final mono-lith. In general, larger pores are obtained in a poorer sol-vent due to an earlier onset of phase separation. Theporogenic solvent controls the porous properties of themonolith through the solvation of the polymer chains inthe reaction medium during the early stages of the poly-merization [34, 36].

    A large number of solvents has already been used to cre-ate the desired macroporosity in rigid monoliths [34, 36,59]. Supercritical carbon dioxide is the newest contribu-

    J. Sep. Sci. 2004, 27, 747766 i 2004WILEY-VCH Verlag GmbH&Co. KGaA,Weinheim

    Figure 1. Morphology and differen-tial pore size distribution curves ofpoly(glycidyl methacrylate-co-ethyl-ene dimethacrylate) beads andmonolith prepared from identicalpolymerization mixtures (adaptedfrom [58]). Polymerization mixture:glycidyl methacrylate 24%, ethylenedimethacrylate 16%, porogenic sol-vent cyclohexanol 48%, dodecanol12%, AIBN 1% (with respect tomonomers), temperature 708C,time 12 h. The pore size distributionwas determined by mercury intru-sion porosimetry; micrographs wereobtained using scanning electronmicroscopy.

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    tion to the broad family of porogenic solvents [60, 61]. Thistype of porogen is attractive since it is non-toxic, non-flam-mable, and inexpensive. In addition, the properties of thissolvent can...


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